Identification of the shared gene signatures and biological mechanism in type 2 diabetes mellitus and hepatocellular carcinoma

Introduction:
Type 2 diabetes mellitus (T2DM) is closely related to hepatocellular carcinoma (HCC). The pathophysiological mechanism of coexistence of T2DM and HCC is unclear. The study aimed to investigate the core genes and pathways involved in the development and progression of T2DM and HCC.

Material and methods:
Datasets for T2DM and HCC were downloaded from the GEO to screen differentially expressed genes (DEGs). Protein–protein interaction (PPI) network analysis was performed on these DEGs to explore their functions and verify hub genes. These genes were validated by quantitative real-time polymerase chain reaction (qRT-PCR) and UALCAN analysis based on The Cancer Genome Atlas (TCGA). Finally, the transcription factor (TF)-miRNA-target gene network was constructed with hub genes, and visualized using Cytoscape software 3.6.1.

Results:
A total of 77 common DEGs were identified. KEGG enrichment revealed that pathways of metabolic processes are enriched in T2DM and HCC. Combining the results of MCODE and CytoHubba showed that AASS, SDS, HAL, KYNU and TDO2 were hub genes. Then, we verified the above results by UALCAN analysis and qRT-PCR. Compared with normal liver tissues, the expression levels of 5 hub genes based on tumor grade were lower in liver hepatocellular carcinoma (LIHC) tissues. mRNA levels of these genes were significantly down-regulated in HepG2 and SNU-449 compared with LO2 cells. Furthermore, we depicted the TF-miRNA-gene interaction network.

Conclusions:
This study proposed a strategy for exploring pathogenic mechanisms of T2DM and HCC. Network hub genes hold promise as disease status biomarkers and treatment targets for alleviating both T2DM and HCC.